Fig. 2

During the first step of attachment, the Crimean-Congo Hemorrhagic Fever Virus (CCHFV) enters the host cytoplasm by relying on clathrin-dependent and pH-dependent mechanisms, which occur in stages 2 and 3, respectively. Upon entering the cytoplasm, viral genomes convert into positive-sense mRNA via the action of the RdRP enzyme. This mRNA then triggers the translation process, leading to the synthesis of viral proteins. Furthermore, these proteins collaborate to generate fresh negative-sense viral genomes enveloped with NP and a bound L protein to commence replication upon infecting the subsequent cell (stage 4). The GPC is transported into the endoplasmic reticulum (ER) and undergoes proteolytic processing through the ER and Golgi apparatus. This processing results in the production of mature GP, as well as the accessory proteins MLD, NSm, and GP38. Recently generated genomes are enclosed inside enveloped particles and the virus emerges from the Golgi apparatus to be released via the secretory route (stage 5). Subsequently, newly formed viral particles are discharged to invade other cells, while GP160/85, MLD, and GP38 are also discharged outside the cells, although the outcome of this release remains uncertain (stage 6). CCHFV proteins not only promote viral multiplication but also inhibit host apoptosis and innate immune mechanisms. The CCHFV NP can impede the intrinsic process of apoptosis at a stage that has not yet. In contrast, the CCHFV NSs facilitate apoptosis by disrupting the mitochondrial membrane or the extrinsic apoptotic pathways. CCHFV may induce apoptosis by generating tumor necrosis factor (TNF) and activating the TNF death receptor pathway. The CCHFV NP is likewise cleaved by host caspase 3, however the presence of oligomeric conformations may hinder this cleavage process. The OTU domain of the CCHFV L protein inhibits the start of the type I interferon response by its deubiquitylating action, suppressing the RIG-I-dependent pathway. MAVS refers to the mitochondrial antiviral signaling protein, whereas vRNA stands for viral RNA [2]